Nuclear WRAP53 promotes neuronal survival and functional recovery after stroke

Failure of neurons to efficiently repair DNA double-strand breaks (DSBs) contributes to cerebral damage after stroke. However, the molecular machinery that regulates DNA repair in this neurological disorder is unknown. Here, we found that DSBs in oxygen/glucose-deprived (OGD) neurons spatiotemporally correlated with the up-regulation of WRAP53 (WD40-encoding p53-antisense RNA), which translocated to the nucleus to activate the DSB repair response. Mechanistically, OGD triggered a burst in reactive oxygen species that induced both DSBs and translocation of WRAP53 to the nucleus to promote DNA repair, a pathway that was confirmed in an in vivo mouse model of stroke. Noticeably, nuclear translocation of WRAP53 occurred faster in OGD neurons expressing the Wrap53 human nonsynonymous single-nucleotide polymorphism (SNP) rs2287499 (c.202C>G). Patients carrying this SNP showed less infarct volume and better functional outcome after stroke. These results indicate that WRAP53 fosters DNA repair and neuronal survival to promote functional recovery after stroke

Aplicaci\uf3n de un algoritmo de split-window para la estimaci\uf3n de la temperatura de la superficie terrestre desde datos AVHRR-NOAA

The estimation of land surface temperature, in partial to completely cloudless clear days, was estimated using data from the Advanced Very High Resolution Radiometer (AVHRR) sensor aboard the satellites of the series National Oceanic and Atmospheric Administration (NOAA) for application of an algorithm based the Split Window's method. The utilized algorithm presupposes corrections for emissivity and the total atmospheric water vapour, and it was validated with field measurements of surface temperature. To this end an LI-1000 data logger was installed at the Agrometeorology Station dependent of the National Institute of Agricultural Research, Carillanca Regional Research Center Carillanca, Araucan\ueda Region of the Araucan\ueda (38\ub041' S lat; 72\ub025' W long; 200 m.o.s.l.). The measurements of temperature were realized at time intervals of one hour. Obtained results showed that the application of the algorithm permits obtaining the land surface temperature with a high grade degree of confidence, having a root mean square error (RMSE) inferior to 1%.Estimaciones de temperatura de la superficie terrestre, en d\uedas parciales a completamente despejados, fueron realizadas a partir de los datos proporcionados por el sensor Advanced Very High Resolution Radiometer (AVHRR), a bordo de la serie de sat\ue9lites de la National Oceanic and Atmospheric Administration (NOAA) por aplicaci\uf3n de un algoritmo basado en el m\ue9todo de Split-Window. El algoritmo utilizado supone correcciones por emisividad y contenido de vapor de agua atmosf\ue9rico, y fue validado con mediciones de temperatura de la superficie terrestre realizadas en terreno. Para esto, un data logger LI-1000 se instal\uf3 en la Estaci\uf3n Agrometeorol\uf3gica dependiente del Instituto de Investigaciones Agropecuarias, Centro Regional de Investigaci\uf3n Carillanca, Regi\uf3n de la Araucan\ueda (38\ub041'lat. S; 72\ub025'long. O; 200 m.s.n.m). Las mediciones de temperatura se realizaron a intervalos temporales de una hora.Los resultados obtenidos muestran que la aplicaci\uf3n del algoritmo permite obtener la temperatura de la superficie terrestre con un alto grado de confianza, obteni\ue9ndose un error cuadrado medio de la predicci\uf3n (RMSE) inferior al 1%

Antihyperthermic treatment decreases perihematomal hypodensity

OBJECTIVE: To investigate the effect on perihematomal hypodensity and outcome of a decrease in body temperature in the first 24 hours in patients with intracerebral hemorrhage (ICH). METHODS: In this retrospective study on a prospectively registered database, among the 1,100 patients, 795 met all the inclusion criteria. Temperature variations in the first 24 hours and perihematomal hypodensity (PHHD) were recorded. Patients >/=37.5 degrees C were treated with antihyperthermic drugs for at least 48 hours. The main objective was to determine the association among temperature variation, PHHD, and outcome at 3 months. RESULTS: The decrease in temperature in the first 24 hours increased the possibility of good outcome 11-fold. Temperature decrease, lower PHHD volume, and a good outcome were observed in 31.8% of the patients who received antihyperthermic treatment. CONCLUSION: The administration of early antihyperthermic treatment in patients with spontaneous ICH with a basal axillary temperature >/=37.5 degrees C resulted in good outcome in a third of the treated patients

Influence of Sex on Stroke Prognosis: A Demographic, Clinical, and Molecular Analysis

Identifying the complexities of the effect of sex on stroke risk, etiology, and lesion progression may lead to advances in the treatment and care of ischemic stroke (IS) and non-traumatic intracerebral hemorrhage patients (ICH). We studied the sex-related discrepancies on the clinical course of patients with IS and ICH, and we also evaluated possible molecular mechanisms involved. The study's main variable was the patient's functional outcome at 3-months. Logistic regression models were used in order to study the influence of sex on different inflammatory, endothelial and atrial dysfunction markers. We recruited 5,021 patients; 4,060 IS (54.8% male, 45.2% female) and 961 ICH (57.1% male, 42.9% female). Women were on average 5.7 years older than men (6.4 years in IS, 5.1 years in ICH), and more likely to have previous poor functional status, to suffer atrial fibrillation and to be on anticoagulants. IS patients showed sex-related differences at 3-months regarding poorer outcome (55.6% women, 43.6% men, p < 0.0001), but this relationship was not found in ICH (56.8% vs. 61.9%, p = 0.127). In IS, women had higher levels of NT-proBNP and 3-months worse outcome in both cardioembolic and non-cardioembolic stroke patients. Stroke patients showed sex-related differences in pre-hospital data, clinical variables and molecular markers, but only IS patients presented independent sex-related differences in 3-months poor outcome and mortality. There was a relationship between the molecular marker of atrial dysfunction NT-proBNP and worse functional outcome in women, resulting in a possible indicator of increased dysfunction

Intra- and extra-hospital improvement in ischemic stroke patients: influence of reperfusion therapy and molecular mechanisms

Neuroprotective treatments in ischemic stroke are focused to reduce the pernicious effect of excitotoxicity, oxidative stress and inflammation. However, those cellular and molecular mechanisms may also have beneficial effects, especially during the late stages of the ischemic stroke. The objective of this study was to investigate the relationship between the clinical improvement of ischemic stroke patients and the time-dependent excitotoxicity and inflammation. We included 4295 ischemic stroke patients in a retrospective study. The main outcomes were intra and extra-hospital improvement. High glutamate and IL-6 levels at 24 hours were associated with a worse intra-hospital improvement (OR:0.993, 95%CI: 0.990-0.996 and OR:0.990, 95%CI: 0.985-0.995). High glutamate and IL-6 levels at 24 hours were associated with better extra-hospital improvement (OR:1.13 95%CI, 1.07-1.12 and OR:1.14, 95%CI, 1.09-1.18). Effective reperfusion after recanalization showed the best clinical outcome. However, the long term recovery is less marked in patients with an effective reperfusion. The variations of glutamate and IL6 levels in the first 24 hours clearly showed a relationship between the molecular components of the ischemic cascade and the clinical outcome of patients. Our findings suggest that the rapid reperfusion after recanalization treatment blocks the molecular response to ischemia that is associated with restorative processes

Regulatory T cells participate in the recovery of ischemic stroke patients

BACKGROUND: Recent preclinical studies have shown that regulatory T cells (Treg) play a key role in the immune response after ischemic stroke (IS). However, the role of Treg in human acute IS has been poorly investigated. Our aim was to study the relationship between circulating Treg and outcome in human IS patients. METHODS: A total of 204 IS patients and 22 control subjects were recruited. The main study variable was good functional outcome at 3 months (modified Rankin scale </=2) considering infarct volume, Early Neurological Deterioration (END) and risk of infections as secondary variables. The percentage of circulating Treg was measured at admission, 48, 72 h and at day 7 after stroke onset. RESULTS: Circulating Treg levels were higher in IS patients compared to control subjects. Treg at 48 h were independently associated with good functional outcome (OR, 3.5; CI: 1.9-7.8) after adjusting by confounding factors. Patients with lower Treg at 48 h showed higher frequency of END and risk of infections. In addition, a negative correlation was found between circulating Treg at 48 h (r = - 0.414) and 72 h (r = - 0.418) and infarct volume. CONCLUSIONS: These findings suggest that Treg may participate in the recovery of IS patients. Therefore, Treg may be considered a potential therapeutic target in acute ischemic stroke

El estatuto can\uf3nico de los indios en el Primer S\uednodo Diocesano de Yucat\ue1n (1722) /

Contiene: t. I-II